This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Manganese redox chemistry is fundamental to biological processes at molecular,cellular and environmental scales, from antioxidant defense to oxygenicphotosynthesis. Biomedically important enzymes including Mn superoxide dismutase(MnSOD), Mn catalase (MnC), and oxalate oxidase (OXO) require a catalytic manganesecofactor for their biological function, yet the molecular mechanisms involved indelivering the essential metal ion are just beginning to be studied in detail. The goal of this project is to advance our understanding of the biochemicalmechanisms responsible for the metal-binding maturation of the ubiquitous andessential antioxidant metalloezyme, MnSOD. This work is fundamental to understandingthe role of manganese trafficking in human health and disease. Further,understanding the metal binding mechanism of this Mn metalloenzyme may contributenew insight into biological defenses against oxidative stress, a key factor in agingand neurodegenerative disorders. This work may also shed light on diseases of metalhomeostasis in which metal misincorporation occurs.